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Chapter VI

Contents

CHAPTER VI

Treatment of Lower Nephron Nephrosis

It should be stated at once that treatment of posttraumatic renal insufficiency after the syndrome has become established is disappointing although not hopeless. Evidence has been presented that shock is one factor important in its etiology. As soon as the patient becomes available for treatment, the shock state can usually be corrected fairly rapidly. Primary treatment of the wounded should therefore be directed toward prompt and adequate resuscitation of every man in shock in order to prevent, if possible, development of serious renal insufficiency.

In presenting our experience in the management of patients with posttraumatic renal insufficiency, certain therapeutic errors to be avoided will be stressed and the use of various drugs and procedures to stimulate renal function (most of which are of questionable value) will be discussed.

Fluid Intake

Early in the Italian campaign fatal cases of posttraumatic renal insufficiency began to appear. Therapy almost universally consisted of intravenous administration of large quantities of various crystalloids. Practically every known diuretic was also employed, and attempts were frequently made to alkalinize the urine by administering large quantities of available base by mouth or vein. In the absence of adequate output of urine, the renal insufficiency soon became complicated by cardiac failure as a result of overloading the circulatory system. The majority of patients so treated died rather promptly of pulmonary edema before they had an opportunity either to die in uremia or to regain adequate renal function.


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Early in the course of our study it was found that those patients with renal insufficiency almost without exception had increased plasma volumes, as was shown in Chapter V. Here then was an additional explanation for the frequency of pulmonary edema; we were dealing with patients who, as a result of renal failure, already had a circulating plasma volume larger than normal. If additional fluids were added, especially those containing sodium, water retention became more severe. The frequency of pulmonary edema and cardiac failure is therefore not surprising. The therapeutic implications of these physiologic abnormalities are clear. Patients with this type of renal insufficiency already have too much extracellular fluid and too large a plasma volume, apparently primarily as a result of the kidney's being unable to excrete this surplus water. Treatment should therefore include (1) any judicious measures which might possibly encourage the kidneys to excrete more urine, and (2) avoidance of any measures which would further increase plasma volume and secondarily cause cardiac embarrassment.

As was shown in the previous chapter, the critical period in the majority of patients with renal insufficiency appeared to be the first 10 days after wounding, when 94 percent of the total deaths occurred. Evidence has been presented that renal function had begun to improve after this time in a number of patients, even though they subsequently died in uremia. Thus the importance of preventing an early fatal outcome resulting from too enthusiastic fluid administration cannot be overemphasized. Unfortunately most of these patients eventually die in uremia regardless of treatment, but by judicious use of fluids they are at least allowed an opportunity to recover renal function spontaneously and their chance of survival is increased.

In cases in which fluids were restricted, the incidence of pulmonary edema was, in our considered judgment, materially lessened, even in those patients who subsequently died primarily of renal failure. A few who recovered (Cases 43, 44, and 138) might have died of heart failure if quantities of fluid comparable to those previously employed had been given.

Our recommendation on fluid intake for the average patient with oliguria or anuria is that ordinarily not more than from 500 to 1,000 cubic centimeters in excess of urinary output be given daily. The patients in this study were seen in the fall, winter, and spring months when the temperature in Northern Italy was such that extrarenal fluid losses were probably minimal. In hot weather or when sweating is excessive this allowance should probably be increased. If


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urinary output increases to more than 1 liter daily, it is suggested that intake of fluids parallel or slightly exceed output of urine until retained nitrogen is cleared. Oral fluids, whenever their use is feasible, are preferred to parenteral ones in order to avoid sudden augmentation of the already increased plasma volume. Such parenteral fluids as are used should be administered slowly, and the patient should be carefully observed for signs of pulmonary edema during infusion. For reasons to be mentioned later under Hypertonic Solutions, the preferred parenteral fluid is an isotonic solution of dextrose.1

We have too little data on sodium to compare the level of this cation in the serum with the sodium intake. Hence it cannot be stated whether hyponatremia accompanied the hypochloremia, and therefore whether serious sodium depletion ever occurred. It now appears that as a consequence of the practice of giving almost no salt parenterally, hypochloremia resulted in some patients, although the outcome in those with decreased plasma chlorides apparently was no different from that in patients with normal chlorides. In our opinion, once posttraumatic renal insufficiency has become established, the danger of producing further edema and circulatory failure exceeds the questionable benefit to be derived from continued attempts to replenish deficient sodium by administration of sodium salt. We would therefore now recommend that during the oliguric and anuric phase salt be given only in quantities sufficient to replace extrarenal salt losses and the small quantity lost in the urine. These combined losses can only be estimated; they probably would seldom exceed one or two grams of salt daily.

Procedures and Drugs Used to Stimulate Kidney Function

Our experience revealed no positive and sure measures capable of re-establishing kidney function after renal insufficiency had developed. The aim should always be to avoid measures that might be harmful during the period before

    1Because of the water-retaining property of the cation in sodium chloride, we suggested that the largest portion of the parenteral fluids given consist of 5- or 10-percent dextrose in distilled water. However, only the 10-percent prepared solution was available during most of the period when these studies were being made. Although 5-percent dextrose can be made up by adding dextrose solution to distilled water, under field conditions and the pressure of work during combat this is troublesome and was not often done.


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the kidneys spontaneously begin to clear retained waste products. Well-known methods of stimulating urine flow that were tried will be discussed briefly. It is evident from the results that they were of no value, or at best of questionable value.

Hypertonic Solutions

The advisability of giving hypertonic solutions parenterally in this syndrome is highly debatable. They exert, at least in the presence of normal renal function, a diuretic effect by (1) temporarily increasing plasma volume, and (2) by limiting tubular reabsorption of water due to the osmotic effect of increased concentration of solute in the distal tubules. It is clear that the first of these actions is undesirable, since the circulating plasma volume is already increased; the second is desirable if tubular reabsorption can be altered in the damaged kidney.

Hypertonic saline (10-percent) solution was used in only one patient--the only one in our series with a true transfusion incompatability (Case 9). There was no observed effect on urinary output. It might be argued that early trial of such a solution would be of value in this type of renal insufficiency. If there is no response to 500 cc. of 3-percent saline solution, further attempts at diuresis by this method surely are contra-indicated because of the undesirable increase in plasma volume which must result from excessive salt administration.

Either a hypertonic dextrose solution or 5-percent dextrose in isotonic saline solution was the parenteral fluid most often given to the patients we observed. When solutions rendered hypertonic by sugar are employed, the osmotic effect on the plasma volume must be transient, lasting only until the dextrose is metabolized. The dextrose aids in nourishing patients who, as a rule, are eating poorly or not at all. The concentration of dextrose employed in hypertonic solution varied from 10 to 50 percent, but the 10-percent solution was the one most often used. There was little if any evidence from extensive use of these forms of hypertonic solutions that they influenced the output of urine.

In summary, since hypertonic solutions may dangerously increase plasma volume, and moreover since our data indicate they are ineffective in promoting urinary flow, isotonic solutions would seem to be preferable. If hypertonic solutions are employed, as they occasionally are in oliguria, dextrose is usually the one of choice; limited trial of hypertonic saline solution might be indicated in some cases.


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Alcohol

The known diuretic effect of alcohol, and the suggestion that its administration might increase renal blood flow2 prompted a rather extensive trial of this agent. It was given to 22 patients, 20 of whom subsequently died of renal insufficiency and 2 of whom survived through the mechanism of recovery diuresis. Usually is was given intravenously, slowly, as a 5-percent solution, the total daily dose being from 50 to 100 cc. of 95-percent ethyl alcohol. As an alternative, if the patient could tolerate it, from 120 to 180 cc. of whiskey were given by mouth daily. Of the 20 patients who died, 7 received approximately these doses for 1 day only, 9 for 3 to 4 days, and 4 for 5 to 8 days. Records are not available of the total quantities received by the 2 patients who recovered, but it is known that they received similar daily doses. No symptoms due to the alcohol, other than occasional mild euphoria and drowsiness, were observed in any patient.

In only 2 of the 20 patients who died (Cases 41 and 52) was there a significant increase in urinary output following the use of alcohol. The 2 patients who recovered had marked diuresis. Other patients showed no significant effects, although occasional transitory increases of as much as 300 cc. per day in urinary output were noted. Similar increases, however, occurred in patients with renal insufficiency who had not been given alcohol.

Mercurial Diuretics

Mercupurin, in doses of 1 or 2 cc., was given to three patients who subsequently died of renal failure. No diuretic effect was demonstrable.

Aminophylline

No demonstrable diuresis resulted from intravenous administration of 0.24 to 0.48 Gm. of this drug to four patients who later died of renal failure.

Inorganic Ions

The use of sodium chloride has been mentioned under "Fluid Intake" and Hypertonic Solutions.

    2LAUSON, H. D.; BRADLEY, S. E. and COURNAND, A.: Renal circulation in shock. J. Clin. Investigation 23: 381-402, May 1944.


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Sodium sulfate in isotonic (3.2 percent) or hypertonic (4.2 percent) solution was given to two patients in total doses of 800 cc. and 1,000 cc. respectively. Neither any beneficial nor harmful effects were observed. Both patients subsequently died in renal failure.

Magnesium sulfate and potassium chloride were employed on the theory that these solutions might be effective in reducing edema of renal tubular cells and hence perhaps promoting urinary flow. Magnesium sulfate was used in four patients (Cases 69, 78, 93, and 95). From 3 to 8 Gm. were given daily (as 50-percent solution intravenously and intramuscularly) for periods of from 2 to 5 days. Plasma magnesium levels, determined in two of these patients, were 7.0 milliequivalents per liter after 24 Gm. of magnesium sulfate had been administered in 4 days in one (Case 93), and 3.8 milliequivalents per liter after 8 Gm. had been given in 2 days in the other (Case 95). This second patient received in addition 10 Gm. of potassium chloride (as 0.5-percent solution intravenously) at about the same time. No increase in output of urine was demonstrated in these patients and all four died of typical renal failure.

Although no definite symptoms of toxicity due to these cations were demonstrable in these four patients, we believe that the use of magnesium and potassium in such cases is dangerous. In the presence of renal failure, administration of magnesium results in a rapid rise in the plasma concentration of this ion. The danger of reaching toxic levels, it is believed, outweighs any possible beneficial effects. We have no data on potassium levels reached in the one patient who received potassium chloride. However, because this ion likewise exerts toxic effects, in our opinion it should not be used in such cases unless serum potassium levels are known to be normal or low. There is some evidence in the literature to support the contention that retained potassium may play a lethal role in uremia.3

Alkalis

The effect of alkalis in wounded patients will be discussed in detail in Chapter VII. Alkalis were given, usually in small doses, to many of the patients after renal insufficiency had developed. Eleven patients who later died of uremia were given between 10 and 20 Gm. of sodium bicarbonate per day for 2 or more days, yet in only two of these patients was an alkaline urine observed. The

    3HOFF, H. E.; SMITH, P. K., and WINKLER, A. W.: Cause of death in experimental anuria. J. Clin. Investigation 20: 607-624, November 1941.


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dangers of adding sodium to the extracellular fluid have been discussed. Further, the main reason for giving it in renal insufficiency is to produce an alkaline urine, the therapeutic value of which is debatable. We found no evidence that the use of alkalis has any place in the therapy of established posttraumatic renal insufficiency; in fact it may cause further harm.

Spinal Anesthesia

For many years, whenever anuria developed, it had been customary to suggest that spinal anesthesia be induced in the belief that the kidney failure might perhaps be accounted for, at least in part, by reflex vascular spasm and that this could be interrupted by spinal anesthesia. The results on the whole have been discouraging. Recent information suggests that part of the innervation of the kidney may come from higher origins than was earlier supposed. For this reason, anesthesia to the level of the clavicle was planned. With sensory anesthesia to this level, it is probable that vasomotor anesthesia was higher than this, since it is produced by a lower concentration of procaine hydrochloride than is required for sensory anesthesia. Pertinent data from four cases4 in this study in which this procedure was tried are summarized briefly as follows.

Case Summaries

1. (Case 47)-In 22 hours preceding high spinal anesthesia this patient had voided 30 cc. of urine. The bladder was empty at the time anesthesia was induced.

    0800 hours -Blood pressure 128/90.
    0820 " -175 mg. procaine hydrochloride in 4 cc. spinal fluid were injected into the third lumbar interspace. Height achieved by barbotage.
    0830 " -Blood pressure 135/88.
    0835 " -Blood pressure 118/80.
    0843 " -Blood pressure 120/80.
    0830 " -Sensory anesthesia (pinprick) was present to the top of the second rib at the sternum.
    0850 " -Blood pressure 112/80.
    0915 " -Blood pressure 118/80. Sensory anesthesia persisted at the same level as at 0830.
    0925 " -Blood pressure 118/80.
    0945 " -Sensory anesthesia was beginning to wear off. There was no respiratory impairment at any time.

    4Capt. Gerald Shortz of the 2d Auxiliary Surgical Group carried out the spinal anesthesias on three of these patients.


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The patient was catheterized 5½ hours after the spinal anesthesia had been induced. The bladder was still empty. Conclusion: The anesthesia had no diuretic effect.

2. (Case 95)-The details concerning this case are similar to those of Case 47, except that in this one anesthesia was obtained to about the nipple line, where it persisted for 70 minutes. The blood pressure did not fall during the period of anesthesia. Sixty-five cc. of urine were present in the bladder just before induction of anesthesia. In the 24 hours following induction of anesthesia there was no formation of urine; this was checked by catheter.

3. (Case 135)-In 8 hours preceding spinal anesthesia 65 cc. of urine had formed and were obtained by catheter just before anesthetization.

    1410 hours -180 mg. procaine hydrochloride in 10 cc. of spinal fluid were injected into the third lumbar interspace.
    1415 " -Anesthesia was present to the eighth cervical vertebra.
    1430 " -Anesthesia was present to the fourth thoracic vertebra.
    1500 " -Anesthesia was present to the seventh thoracic vertebra.
    1515 " -Anesthesia was present to the ninth thoracic vertebra.
    1535 " -Anesthesia was present to the second lumbar vertebra.
    1600 " -Anesthesia of the saddle area and legs only.
    1630 " -Full recovery.
    2015 " -85 cc. of urine were obtained by catheterization.

There was no fall of blood pressure during this test. Since 65 cc. of urine had been formed in 8 hours preceding anesthesia, and 85 cc. in 6 hours following, no definite effect could be attributed to the anesthesia.

4. (Case 138)-In 11 hours preceding spinal anesthesia, 40 cc. of urine had been formed. The bladder was emptied of this just before anesthesia was induced. The blood pressure remained at 120/72 throughout the test.

    1500 hours -200 mg. procaine hydrochloride were dissolved in 12 cc. of spinal fluid and injected into the third lumbar interspace.
    1505 " -Anesthesia was present to the eighth cervical vertebra.
    1515 " -Anesthesia was present to the fifth thoracic vertebra.
    1535 " -Anesthesia was present to the second lumbar vertebra.
    1600 " -Saddle and leg anesthesia only.
    1650 " -Complete recovery.
    2100 " -60 cc. of urine were obtained by catheterization.

Sixty cc. of urine were excreted in 6 hours following induction of anesthesia and 40 cc. had been formed in 11 hours preceding anesthesia; hence no definite effect of the spinal anesthesia was evident. The patient's low point in output was 2 days preceding the anesthesia; in other words, a steady increase in urinary output had already begun. This patient was the only one of this group who


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recovered. One cannot say that the spinal anesthesia either did or did not play a part in his recovery.

No definite evidence was obtained from the four patients studied that spinal anesthesia influenced the output of urine. We had planned to try this procedure earlier, that is, soon after the onset of progressive oliguria. These plans were interrupted by the end of the war in Italy.

Kidney Decapsulation, Sympathectomy

This was carried out in one patient (Case 129) 54 hours after initial operation, during which time the patient had voided 150 cc. of urine. The right kidney was decapsulated and a periarterial sympathectomy performed. There was no effect on urinary output, and the patient died in uremia 48 hours later, having excreted 180 cc. of urine since the second operation.

Correction of Anemia

In instances in which whole blood transfusions were indicated for the correction of severe anemia, these were given. Relatively fresh bank blood was used to avoid possible pigment insult secondary to intravascular hemolysis of aged cells. No benefit or detriment to the already failing kidney was observed.

Nutrition

Ideally, nutritive requirements during the acute phase of the syndrome should be met by an adequate caloric intake, but with such foods that there will be minimal destruction of body protein and production of urea nitrogen from exogenous proteins. These demands would best be served by a carbohydrate and fat intake sufficient to furnish from 1,500 to 2,000 calories per day. If the patient is unable to take food by mouth, it is practically impossible to administer enough dextrose intravenously to furnish such a caloric intake and still adhere to the more important rules of restricting fluids and prohibiting hypertonic solutions. During the acute phase of renal insufficiency one must be content with merely furnishing the small requirement of sodium chloride as isotonic saline solution, and with an attempt to meet caloric requirements by supplying dextrose


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in a 5-percent solution in water in the additional small fluid allowance remaining--that is, a total daily intake of 500 to 1,000 cc. in excess of total urinary output.

SUMMARY

Various procedures were tried in the treatment of lower nephron nephrosis which occurred as a complication in severely wounded men. Among these were control of fluid intake, the use of relatively fresh blood for transfusions to combat anemia, attempts to make the urine alkaline, spinal anesthesia, kidney decapsulation, and the administration of a number of drugs commonly believed to stimulate the excretion of urine. Except for evidence that avoiding excess fluid administration reduced the incidence of early death from pulmonary edema, all were essentially disappointing, leading to the conclusion that "the best treatment of posttraumatic renal insufficiency is its prevention." Since shock is known to be a major factor in its development, prompt and adequate resuscitation of every man in shock is most important.

Once renal insufficiency has developed, avoidance of the therapeutic error of administering too much fluid and hence accentuating an already increased plasma volume becomes of first importance. Types and quantities of fluids to be administered during the period when renal failure is most severe (usually the first 10 days after trauma) have been recommended. Although we employed various drugs or procedures directed toward promoting urine flow or improving kidney function, we met with little success in their use. These measures included the use of hypertonic solutions, alcohol, mercurial and xanthine diuretics, and solutions of various inorganic ions, the induction of spinal anesthesia, and decapsulation of a kidney. The essential requirement appears to be that of tiding the patient over the critical period until natural recovery of renal function begins. Dialysis procedures, which attempt to remove waste products by routes other than the kidneys until the kidneys resume their function, offer possibilities that were not tried in this study.

CASES OF SPECIAL INTEREST IN THIS CHAPTER

9 43 47 69 93 129

41 44 52 78 95 135 138

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